Point mutation of Arg440 to His in cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency.

Abstract

Genetic disorders in the gene encoding P450c17 cause 17 alpha-hydroxylase deficiency. The consequent defects in the synthesis of cortisol and sex steroids cause sexual infantilism and a female phenotype in both genetic sexes as well as mineralocorticoid excess and hypertension. A 15-yr-old patient from Germany was seen for absent pubertal development and mild hypertension with hypokalemia, high concentrations of 17-deoxysteroids, and hypergonadotropic hypogonadism. Analysis of her P450c17 gene by polymerase chain reaction amplification and direct sequencing showed mutation of codon 440 from CGC (Arg) to CAC (His). Expression of a vector encoding this mutated form of P450c17 in transfected nonsteroidogenic COS-1 cells showed that the mutant P450c17 protein was produced, but it lacked both 17 alpha-hydroxylase and 17,20-lyase activities. To date, 15 different P450c17 mutations have been described in 23 patients with 17 alpha-hydroxylase deficiency, indicating that mutations in this gene are due to random events.

• Authors: C E Fardella, D W Hum, J Homoki, W L Miller
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 79 Issue 1 Pg. 160-4 (Jul 1994) ISSN: 0021-972X [Print] United States
• PMID: 8027220 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Histidine
• Arginine
• Steroid 17-alpha-Hydroxylase

Topics

• Adolescent
• Adrenal Hyperplasia, Congenital
• Arginine (genetics)
• Base Sequence
• Cell Line
• Female
• Germany
• Histidine (genetics)
• Humans
• Hypertension (etiology)
• Hypokalemia (etiology)
• Molecular Sequence Data
• Mutagenesis, Site-Directed
• Point Mutation
• Polymerase Chain Reaction
• Steroid 17-alpha-Hydroxylase (genetics, metabolism)
• Transfection